Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt.

In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan(©)), and serum markers (APRI, Fib4 and Fibrotest(©)). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.

Vein of Galen aneurysmal malformation associated with brain abscess: A computed tomography case report.

Vein of Galen malformation (VGM) is a rare congenital, uncommon intracerebral vascular anomaly rarely complicated with the development of brain abscess as secondary to primary infection or after endovascular treatment. We report a very rare finding of a vein of Galen aneurysm associated with a large brain abscess at the time of diagnosis. A 12-year-old boy with a high-grade fever, severe headache, and recurrent episodes of convulsions came into the radiology department of Kassala Advanced Diagnostic Center. On a Siemens 16-slice scanner, brain non-contrast enhanced computed tomography (NECT) and contrast enhanced CT (CECT) was used to determine the source of the acute headache and convulsions which revealed a right frontal peripherally enhancing cystic lesion measuring 5.7 × 4.7 × 5.3 cm2 surrounded by massive vasogenic edema causing mass effect with midline shift to the left side by 1.5 cm suggestive of brain abscess. There is evidence of another avidly enhancing lesion seen within the third ventricle continuous with a straight sinus surrounded by extensive vascular loops consistent with an aneurysm of the vein of Galen, it was causing compression of the cerebral aqueduct with upstream mild hydrocephalus with dilated both lateral ventricles. Late presentation, diagnosis, and treatment also lead to an increase in the morbidities and mortalities of such case conditions. Urgent intervention should be considered for better outcomes.

The impact of different imaging modalities in diagnosis and management of patient with dural arteriovenous fistula: A rare case report.

In vascular neurosurgery, dural arteriovenous fistulas (DAVFs) are a difficult, challenging condition whose natural history and therapy are still debated. This case report presented a 30-year-old male patient who experienced intermittent headaches for two months, along with gradual weakness in all four limbs, resulting in quadriplegia. Magnetic resonance imaging (MRI), computed tomography (CT), and digital subtraction angiography (DSA) played a significant role in the diagnosis of the patient, in which the final diagnosis was vascular myelopathy due to Dural arteriovenous fistula (DAVF). A successful embolization procedure of arteriovenous fistula using balloon-assisted liquid embolic agents, through branches of the right occipital artery was performed, resulting in complete obliteration of the fistula. In order to improve the neurovascular symptoms that had previously been reported, the patient was effectively undergoing rehabilitation, with notable progress.

Multicenter, international study of CT practices and radiation doses from 10 African countries: An International Atomic Energy Agency (IAEA) baseline study.

PURPOSE: The objective of our IAEA-coordinated international study was to assess CT practices and radiation doses from multiple hospitals across several African countries. METHODS: The study included 13 hospitals from Africa which contributed information on minimum of 20 consecutive patients who underwent head, chest, and/or abdomen-pelvis CT. Prior to the data recording step, all hospitals had a mandatory one-hour training on the best practices in recording the relevant data elements. The recorded data elements included patient age, weight, protocol name, scanner information, acquisition parameters, and radiation dose descriptors including phase-specific CT dose index volume (CTDIvol in mGy) and dose length product (DLP in mGy.cm). We estimated the median and interquartile range of body-region specific CTDIvol and DLP and compared data across sites and countries using the Kruskal-Wallis H Test for non-normal distribution, analysis of variance. RESULTS: A total of 1061 patients (mean age 50 ± 19 years) were included in the study. 16 % of CT exams had no stated clinical indications for CT examinations of the head (32/343, 9 %), chest (50/281, 18 %), abdomen-pelvis (67/243, 28 %), and/or chest-abdomen-pelvis CT (24/194, 12 %). Most hospitals used multiphase CT protocols for abdomen-pelvis (9/11 hospitals) and chest CT (10/12 hospitals), regardless of clinical indications. Total median DLP values for head (953 mGy.cm), chest (405 mGy.cm), and abdomen-pelvis (1195 mGy.cm) CT were above the UK, German, and American College of Radiology Diagnostic Reference Levels (DRLs). CONCLUSIONS: Concerning variations in CT practices and protocols across several hospitals in Africa were demonstrated, emphasizing the need for better protocol optimization to improve patient safety.

Relation of Dietary Factors with Infection and Mortality Rates of COVID-19 across the World.

OBJECTIVE: Poor dietary habits are considered to be the second-leading risk factors for mortality and disability-adjusted life-years (DALYs) in the world. Dietary patterns are different based on cultural, environmental, technological, and economic factors. Nutritional deficiencies of energy, protein, and specific micronutrients have been shown to contribute to depressed immune function and increased susceptibility to infections. We aimed to explore the relation of dietary factors with global infection and mortality rates of COVID-19 in this study. DESIGN: In the current ecological study, the countries that had national dietary data from the Global Dietary Databases of the United Nations and coronavirus disease statistics from the World Health Organization (WHO) were included. The countries that had coronavirus disease statistics from the WHO were consecutively checked for the recent data of the dietary factors. SETTING: World. PARTICIPANTS: 158 countries across the world. MEASUREMENTS: infection and mortality rates of COVID-19; dietary factors. RESULTS: The median crude infection and mortality rates by COVID-19 were 87.78 (IQR: 468.03) and 0.0015 (IQR: 0.0059), respectively. The two highest percentage of the crude infection rate were between 0 and 500 (75.9%) and 500-1000 (8.9%) per one million persons. The regression analysis showed that the crude infection rate has been increased by raising consuming fruits (Beta: 0.237; P=0.006) and calcium (Beta: 0.286; P=0.007) and was decreased with rising consuming beans and legumes (Beta: -0.145; P=0.038). The analysis showed that the crude mortality rate was increased by raising consuming sugar-sweetened beverages (Beta: 0.340; P<0.001). Whereas, the crude mortality rate by COVID-19 has been decreased by increasing fruits consuming (Beta: -0.226; P=0.047) and beans and legumes (Beta: -0.176; P=0.046). CONCLUSION: The present study showed the higher intake of fruits and sugar-sweetened beverages had a positive effect on infection and mortally rates by COVID-19, respectively. In contrast, the higher intake of beans and legumes had a negative effect on both increasing infection and mortality rates.

VEGF 165 b, an antiangiogenic VEGF-A isoform, binds and inhibits bevacizumab treatment in experimental colorectal carcinoma: balance of pro- and antiangiogenic VEGF-A isoforms has implications for therapy.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF-A) antibody, is used in metastatic colorectal carcinoma (CRC) treatment, but responses are unpredictable. Vascular endothelial growth factor is alternatively spliced to form proangiogenic VEGF(165) and antiangiogenic VEGF(165)b. Using isoform-specific enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, we found that over 90% of the VEGF in normal colonic tissue was VEGF(xxx)b, but there was a variable upregulation of VEGF(xxx) and downregulation of VEGF(xxx)b in paired human CRC samples. Furthermore, cultured colonic adenoma cells expressed predominantly VEGF(xxx)b, whereas colonic carcinoma cells expressed predominantly VEGF(xxx). However, adenoma cells exposed to hypoxia switched their expression from predominantly VEGF(xxx)b to predominantly VEGF(xxx). VEGF(165)b overexpression in LS174t colon cancer cells inhibited colon carcinoma growth in mouse xenograft models. Western blotting and surface plasmon resonance showed that VEGF(165)b bound to bevacizumab with similar affinity as VEGF(165). However, although bevacizumab effectively inhibited the rapid growth of colon carcinomas expressing VEGF(165), it did not affect the slower growth of tumours from colonic carcinoma cells expressing VEGF(165)b. Both bevacizumab and anti-VEGF(165)b-specific antibodies were cytotoxic to colonic epithelial cells, but less so to colonic carcinoma cells. These results show that the balance of antiangiogenic to proangiogenic isoforms switches to a variable extent in CRC, regulates tumour growth rates and affects the sensitivity of tumours to bevacizumab by competitive binding. Together with the identification of an autocrine cytoprotective role for VEGF(165)b in colonic epithelial cells, these results indicate that bevacizumab treatment of human CRC may depend upon this balance of VEGF isoforms.

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions.

BACKGROUND: VS38c is a monoclonal antibody that recognises a rough endoplasmic reticulum (rER) intracellular antigen termed cytoskeleton-linking membrane protein 63. rER is typically found in viable tumour cells and is abundant in osteosarcoma cells. The aim of this study was to determine the diagnostic and prognostic utility of VS38c in the histological assessment of osteosarcoma and other bone tumours/tumour-like leisons. METHODS: Immunohistochemical staining with VS38c was carried out on formalin-fixed specimens of osteosarcoma (pre/post-chemotherapy) and a wide range of benign and malignant bone lesions. In addition, VS38c staining of cultures of MG63 and Sa0S2 osteosarcoma cell cultures. (±cisplatin and actinomycin D-treatment) was analysed. RESULTS: VS38c strongly stained tumour cells in all low-grade and high-grade osteosarcomas and in undifferentiated sarcomas and high-grade chondrosarcomas. There was little or no VS38c staining of low-grade chondrosarcomas or chordomas and variable staining of Ewing sarcomas. Osteoblasts in benign bone-forming tumours and mononuclear stromal cells in chondroblastomas, giant cell tumours and non-ossifying fibromas strongly stained for VS38c. VS38c staining was absent in cisplatin and actinomycin D treated Sa0S2 and MG63 cells. In specimens of osteosarcoma post-neoadjuvant therapy, VS38c staining was absent in most morphologically necrotic areas of tumor although some cells with pyknotic nuclei stained for VS38c in these areas. Most tumour cells exhibiting atypical nuclear forms were not stained by VS38c. CONCLUSIONS: Our findings show that VS38c is a sensitive but not specific diagnostic marker of osteosarcoma. Staining with VS38c identifies viable osteosarcoma cells, a feature which may be useful in the assessment of percentage tumour necrosis post-neoadjuvant chemotherapy.

A simple device to rapidly prepare whole mounts of murine intestine.

Many mouse models of neoplasia and pre-neoplasia require the examination of whole mounts of the gastrointestinal tract. A simple device has been produced to facilitate the rapid preparation of mouse intestines for subsequent quantification of tumours and pre-neoplastic lesions such as aberrant crypt foci. The device greatly speeds up the production of whole mounts and also provides far more consistent and better-quality preparations.

Insulin-like growth factor II supply modifies growth of intestinal adenoma in Apc(Min/+) mice.

Insulin-like growth factor-II (IGF-II) is an embryonic growth promoter and cell survival factor. IGF-II supply is normally limited by gene expression because transcription occurs predominantly from the paternal allele in mouse and man (maternal imprinting). Excess IGF-II has detrimental systemic and local effects in vivo, promoting somatic overgrowth and an increased frequency of tumors. IGF2 mRNA is overexpressed in colorectal and many other human cancers. In this paper, we show that altered IGF-II supply modifies intestinal tumor growth. Mice genetically altered in the IGF-II system were combined in crosses with ApcMin/+, a murine model of human familial adenomatous polyposis. Depending on genetic background, ApcMin/+ acquires multiple small intestinal adenoma before becoming moribund with anemia. Mice that express excess IGF-II delivered using a bovine keratin 10 promoter (k10Igf2/+) develop a disproportionate overgrowth of colon, uterus, and skin. Combination with ApcMin/+ leads to a 10-fold increase in the number and the diameter of colon adenoma (P<0.0001) compared to ApcMin/+ littermate controls (postnatal day 80), an increased susceptibility to rectal prolapse (41%), and a histological progression to carcinoma. Mice with reduced IGF-II supply, secondary to the disruption of the paternal Igf2 allele (Igf2+m/-p), are 60% the weight of wild-type littermates. Combination with ApcMin/+ leads to a 3-fold reduction in small intestinal adenoma number (P<0.0001) compared to ApcMin/+ littermate controls (postnatal day 150), and a significant decrease in adenoma diameter (P<0.001). With in situ hybridization, we show that Igf2 was expressed in all adenoma irrespective of IGF-II supply. This suggests that there is an increased maternal allele expression of Igf2 (loss of imprinting) in adenoma which form, despite paternal Igf2 allele disruption. We conclude that IGF-II supply is a modifier of intestinal adenoma growth, and we provide genetic evidence for its functional role in colorectal cancer progression.

Dendritic and mast cell involvement in the inflammatory response to primary malignant bone tumours.

BACKGROUND: A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain. METHODS: In this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate. RESULTS: The extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface. DISCUSSION: Our findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate. CONCLUSION: Tumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.

Dentine matrix protein 1 (DMP-1) is a marker of bone formation and mineralisation in soft tissue tumours.

Dentine matrix protein 1 (DMP-1) is a non-collagenous matrix protein found in dentine and bone. It is highly expressed by osteocytes and has been identified in primary benign and malignant osteogenic bone tumours. Bone formation and matrix mineralisation are seen in a variety of benign and malignant soft tissue tumours and tumour-like lesions, and in this study, we analysed immunohistochemically the DMP-1 expression in a wide range of soft tissue lesions (n = 254) in order to assess whether DMP-1 expression is useful in the histological diagnosis of soft tissue tumours. Matrix staining of DMP-1 was seen in all cases of myositis ossificans, fibro-osseous tumour of the digits, extraskeletal soft tissue osteosarcoma and in most cases of ossifying fibromyxoid tumour. DMP-1 was also noted in dense collagenous connective tissue of mineralising soft tissue lesions such as tumoural calcinosis, dermatomyositis and calcific tendinitis. DMP-1 was expressed in areas of focal ossification and calcification in synovial sarcoma and other soft tissue tumours. With few exceptions, DMP-1 was not expressed in other benign and malignant soft tissue tumours. Our findings indicate that DMP-1 is a matrix marker of bone formation and mineralisation in soft tissue tumours. DMP-1 expression should be particularly useful in distinguishing extraskeletal osteosarcoma and ossifying fibromyxoid tumour from other sarcomas and in identifying areas of osteoid/bone formation and mineralisation in soft tissue tumours.

Germ cell cancers in adult males are associated with a history of infantile pyloric stenosis.

Germ cell cancers (GCT) are the most common cancers of young men and are curable in at least 90% of cases. A number of aetiological factors have been identified which predispose to the development of these cancers, such as cryptorchidism and hernia. We report the association of GCT with infantile pyloric stenosis (IPS). The case records from 542 adult males with germ cell cancer arising from any site were screened for a history of pyloric stenosis requiring surgical treatment. Nine cases were observed (expected number = 2.168; chi squared = 21.5 (P < 0.001), standardised ratio = 4.15; 95% confidence interval 1.9-7.88). The recognition of rare associations of germ cell tumours may lead to the identification of genetic and environmental factors involved in their aetiology.

Reversible T-wave abnormality in severe acute asthma: an electrocardiographic sign of severity.

Reversible electrocardiographic (ECG) abnormalities are well recognized in severe acute asthma. Inferior lead T-wave abnormalities have only rarely been reported, and their frequency and significance have not been well documented. We studied 70 consecutive patients with severe acute asthma on admission to hospital and during recovery, in order to examine the frequency and natural history of such changes and to document their relationship to the severity of the attack. Twenty-two patients (34%) had inferior lead T-wave inversion on ECGs performed within 1 h of admission (group 1), whereas the rest did not (group 2). Apart from sinus tachycardia this was the most common ECG abnormality. Patients with inferior T-wave inversion were found to have more severe asthma in terms of degree of pulsus paradoxus, peak expiratory flow rate, forced expiratory volume in 1 s and arterial blood oxygen tension. Ten group 1 and ten group 2 patients underwent two-dimensional echocardiography during the acute phase of their illness and during recovery. Six (60%) group 1 patients showed echocardiographic evidence of right ventricular pressure overload compared with only one (10%) patient in group 2 (P less than 0.02). Following recovery, voluntary hyperventilation and exercise testing in ten group 1 patients failed to reproduce the ECG changes seen on admission. Reversible inferior lead T-wave abnormalities may occur in the severe acute asthma and appear to be related to the severity of the attack.

Extracts and fractions of Thymus capitatus exhibit antimicrobial activities.

Preliminary phytochemical screening of the plant Thymus capitatus exhibited the presence of saponins, resins, flavonoids, essential and fixed oils. Aqueous and ethanolic extracts (10-200 mg/ml) as well as saponin, resin and essential oil of the plant (10-5000 micrograms/ml inhibited the growth of several bacteria and fungi.

Synthesis of quaternary 8-hydroxyquinoline and 8-hydroxyquinaldine-carbamates structurally related to cholinesterase.

The quaternary carbamates were synthesized by reaction of 8-hydroxyquinoline and 8-hydroxyquinaldine with alkylisocyanates, then quaternizing the carbamates produced with alkylhalides, aralkylhalides or sulphate. The UV spectra of the compounds obtained showed lambdamax at 285 nm. The new quaternary carbamates were found to be of high toxicity and parasymapathomimetic activity in white mice.